Synthesis of anhydroglycitol esters of improved colour

ABSTRACT

Diesters of dianhydroglycitols can be prepared by esterification of dianhydroglycitols, anhydroglycitols and/or glycitols with alkylcarboxylic or arylcarboxylic acids in the presence of an acid catalyst, the acid catalyst being a macroporous acid ion exchange resin. If glycitols or monoanhydroglycitols are used as the starting material, the reaction temperature is initially of the order of  120 ° C. and after the dehydration is approximately  140 ° C.

[0001] The invention relates to an improved synthesis of alkyl and arylesters of anhydroglycitol derivatives. These compounds are commerciallyinteresting derivatives of the raw material sorbitol and otherglycitols. The potential applications of these compounds are highlydiverse. Esters of monoanhydrosorbitol (sorbital4) are widely used asemulsifiers (Span, Tween)^(1,2). In addition, esters ofdianhydrosorbitol (isosorbide) have many potential applications: aspreservatives³⁻⁵, lubricants⁶, polymer stabiliser⁷, emulsifier incosmetics⁸ ⁹, dispersing agents for pigments¹⁰ or as plasticisers forvinyl resins¹¹⁻¹⁵.

[0002] The dehydration of sorbitol, as an example of that of theglycitols, is shown in the diagram below:

[0003] The current synthesis methods are usually based on acid-catalyseddirect esterifications, sulphuric acid or p-toluenesulphonic acid beingused as catalyst^(13,14). Base-catalysed reactions are also known;however, the reactions concerned here are usually transesterificationreactions at high temperature (above 200° C.)¹⁶⁻¹⁸. Furthermore, the useof acid ion exchange resins of the gel type as catalyst is alsoreported^(19,20); in this context yields of 61 and 63% for isosorbidedibutyrate and isosorbide dipropionate, respectively, are reported,starting from isosorbide.

[0004] In the case of the direct esterification the reaction equilibriumis shifted by removal of the water of reaction. This can be achieved byazeotropic distillation with toluene or xylene^(13,14,20), or by the useof a vacuum²¹. Yields in excess of 70% diester, starting fromisosorbide, are not achieved with any of the above-mentioned methods.

[0005] The esterification of isosorbide is shown in the followingequation:

[0006] The invention relates to the synthesis of esters ofdianhydrosorbitol and other dianhydroglycitols with high conversion(98-100%) and a substantially improved colour, as a result of whichdistillation of the product can be dispensed with. According to theinvention use is made of a macroporous acid ion exchange resin ascatalyst. In addition, an inert gas, such as nitrogen gas, is preferablydispersed through the reaction mixture in order to accelerate theremoval of the water of reaction. A further improvement is obtained byincreasing the turbulence of the reaction mixture, so that the removalof the water of reaction is further promoted. A reduced pressure of, forexample, 10-50 mbar is also advantageous. The colour of the reactionmixture is substantially improved because the reaction temperature canbe kept below 150° C. Furthermore, addition of activated charcoal to thereaction mixture leads to a further reduction in the colour.

[0007] In addition to dianhydrosorbitol (isosorbide) as startingmaterial it has also proved possible to use anhydrosorbitol (sorbitan)and even sorbitol as starting material. If the reaction temperature inthe initial stage of the reaction is kept low (120-125° C.), selectivedehydration takes place, followed by esterification after raising thereaction temperature to 140-150° C. Giacometti et al. ^(22,23) merelyreported the possibility of in situ formation of anhydrosorbitolderivatives during the esterification of sorbitol withp-toluenesulphonic acid, without specifying experimental details forthis.

[0008] Although ion exchange resins have been used as catalyst in thereaction for the dehydration^(19,21,24) of sorbitol, the conversionswere too low (39-57%) and the reaction times usually too long (2-24hours). Feldmann et al. (DE 3 041 673) reported the dehydration ofsorbitol with the aid of a macroporous ion exchange resin, the water ofreaction being removed with the aid of a stream of nitrogen. Despite thehigh yield of isosorbide (93%), the reaction mixture was severelydiscoloured and the reaction time was long (5 h).

[0009] Matyschok et al.²¹ also reported the synthesis of isosorbideesters with the aid of an acid ion exchange resin of the gel type(Wofatit KPS), in which context it must be mentioned that the alkanoicacids used by them have a short chain and thus high intrinsic acidity(acetic acid, propionic acid, butyric acid). The reported yields are,however, too low to be of industrial relevance (60-70%).

[0010] The process according to the invention preferably relates to thesynthesis of diesters in accordance with the following equation:

[0011] Surprisingly it has been found that a substantially improvedmethod of preparation for dianhydrosorbitol diesters has been developedby a combination of techniques known per se. In view of the increasingindustrial relevance of dianhydrosorbitol diesters, this meets animportant need.

[0012] The process according to the invention can be used for theesterification of glycitols and the monoanhydro and dianhydroderivatives thereof. A glycitol is understood to be a sugar alcoholhaving at least 6 carbon atoms. These include, first of all, sorbitol,mannitol, iditol and other hexitols, but also higher analogues such asheptitols and glycitols derived from the di- and oligo-saccharides, suchas lactitol, maltitol, and the like. The process according to theinvention can also be used for glycitols (sugar alcohols) that cannot beconverted to dianhydro analogues, such as pentitols (xylitol, etc.), inwhich case diesters and higher esters of the monoanhydro analogues(xylitan, etc.) are then formed.

[0013] The esterification can take place with any carboxylic acid, suchas alkanoic acids, alkenoic acids, alkadienoic acids,cycloalkanecarboxylic acids and arenecarboxylic acids. The carboxylicacids can be either straight-chain or branched. Examples are propionicacid, hexanoic acid, octanoic acid, nonanoic acid, decanoic acid, lauricacid, stearic acid, cyclohexanecarboxylic acid, optionally substitutedbenzoic acids, phenylacetic acid, naphthalenecarboxylic acid, etc. Thediesters of C₃-C₂₀ carboxylic acids are particularly advantageous.Mixtures of acids, in particular fatty acids of varying chain length,can also be used.

[0014] The esters of shorter chain carboxylic acids, such as C₃-C₆, canbe used in the main as solvents, those of medium chain length alkanoicacids, in particular of C₆-C₁₂ carboxylic acids, are outstandinglysuitable as plasticisers and the longer chain length, for exampleC₁₂-C₁₈, carboxylic acids are mainly usable as lubricants. If desired,monoesters of dianhydroglycitols can also be obtained by using smalleramounts of fatty acids, for example 1 to 2 mol per mol(anhydro)glycitol. What is concerned in this case is then mainly thepreparation of emulsifiers, such as the monoesters of C₁₂-C₂₀ alkanoicacids or alkenoic acids and monoaryl and monoaralkyl esters.

[0015] The choice of the catalyst resin is important. This is an acidcatalyst resin of the macroporous or macroreticular type. In contrast toresins of the gel type, these are resins with a relatively high degreeof crosslinking and consequently a high porosity. A description ofsuitable resins is to be found in standard works on catalyst resins,such as “Ion Exchangers” by Konrad Dörffier, published by De Gruyter,Berlin, 1991, in particular pages 22-23 thereof. Examples of suitableresins are the commercially available resins, such as Amberlyst-15-wet,Amberlyst-15-dry, Amberlyst-16-wet and Amberlyst-36-dry from Rohm andHaas, and comparable resins from other suppliers.

EXAMPLES General Procedure

[0016] The reaction was carried out in a 2.0 1 four-necked,round-bottomed flask equipped with a gas inlet tube (with glass frit), aPt-100 temperature sensor, a Dean-Starck condenser and a mechanicalstirrer. The mechanical stirrer was equipped with a stainless steelcentrifugal stirrer (60 mm diameter). Stirring was carried out at aspeed of 900 revolutions per minute. Heating of the reactor was achievedusing an Isopad 2.0 l electrical heating jacket, equipped with atemperature control unit. During the reaction nitrogen gas was dispersedthrough the reaction mixture via a gas inlet tube at a flow rate of 400ml per minute. The progress of the reaction was followed both bymeasuring the quantity of water formed over time and by GLCdetermination of the reaction mixture. After complete conversion hadbeen achieved, the reaction mixture was cooled to approximately 60-80°C., after which the catalyst was removed by means of a sieve. Thereaction mixture was then stirred for some time (0.5-1.5 hours) withactive charcoal at 80-100° C. Filtration of this mixture through a glassfilter with Filteraid yielded a pale yellow viscous mixture ofisosorbide diester and alkanoic acid. The excess alkanoic acid was thenremoved by means of vacuum distillation. GLC and ¹³C NMR analysis (ofboth the product and the hydrolysed product) of the product thusobtained showed only the presence of the desired isosorbide diester.Average isolated yields were between 95 and 99%.

Example 1 Synthesis of isosorbide 2,5-di-n-octanoate Using isosorbide asthe Starting Material

[0017] A mixture of isosorbide (292.3 g, 2.00 mol), n-octanoic acid(865.3 g, 6.00 mol, 3 eq) and 40 g Amberlyst 15 (dry) resin was stirredat a constant temperature (see Table 1). After complete conversion hadbeen achieved, the yellow transparent reaction mixture was decolourisedwith active charcoal. The excess n-octanoic acid was then distilled offunder vacuum. The product was a pale yellow transparent viscous liquid(95-98%). TABLE 1 Esterification of isosorbide with n-octanoic acid:reaction times at complete conversion isosorbide acid T reaction time(mol) (eq) (° C.) (hours) colour 1 5 145 6 pale yellow 2 3 120 11 yellow2 3 145 7 yellow

Example 2 Synthesis of isosorbide 2,5-di-2-ethylhexanzoate Usingisosorbide as Tile Starting Material

[0018] A mixture of isosorbide (292.3 g, 2.00 mol), 2-ethylhexanoic acid(865.3 g, 6.00 mol, 3 eq) and 40 g Amberlyst 15 (dry) resin was stirredat a constant temperature (see Table 2). After complete conversion hadbeen achieved, the yellow transparent reaction mixture was decolourisedwith active charcoal. The excess 2-ethylhexanoic acid was then distilledoff under vacuum. The product was a pale yellow transparent viscousliquid (95-98%). TABLE 2 Esterification of isosorbide with2-ethylhexanoic acid reaction times at complete conversion isosorbideacid T time (mol) (eq) (° C.) (hours) colour 1 5 145 13 yellow 2 3 14512 pale yellow 2 3 160 6 yellow

Example 3 Synthesis of isosorbide 2,5 di-n-octanoate Using 1,4-sorbitanas the Starting Material

[0019] A mixture of 1,4-sorbitan, (164.5 g, 1.00 mol), n-octanoic acid(432.7 g, 3.00 mol, 3 eq) and 20 g Amberlyst 15 (dry) resin was stirredat 145° C. Complete conversion was achieved after 8 hours. After removalof the catalyst, the yellow transparent reaction mixture wasdecolourised with active charcoal. ¹³C NMR analysis of the hydrolysedproduct of the reaction mixture indicated only the formation ofisosorbide dioctanoate. Distilling off the excess n-octanoic acid,followed by a second decolourisation, gave a pale yellow product in ayield of 80%.

Example 4 Synthesis of isosorbide 2,5 di-n-octanoate Using sorbitol asthe Starting Material

[0020] A mixture of sorbitol, (364.34 g, 2.00 mol), n-octanoic acid(865.3 g, 6.00 mol, 3 eq) and 40 g Amberlyst 15 (dry) resin was stirredat 125° C. After approximately 4 mol water had been collected(indicative of quantitative dehydration), the temperature was raised to145° C. Complete conversion was achieved after 8 hours. After removal ofthe catalyst, the yellow-brown transparent reaction mixture wasdecolourised with active charcoal. ¹³C NMR analysis of the hydrolysedproduct of the reaction mixture indicated only the presence ofisosorbide dioctanoate.

Example 5 Synthesis of isosorbide 2,5 di-n-octanoate Using isosorbideand Active Charcoal as the Starting Materials

[0021] A mixture of isosorbide (292.3 g, 2.00 mol), n-octanoic acid(865.3 g, 6.00 mol, 3 eq), 40 g Amberlyst 15 (dry) resin and 20g activecharcoal was stirred at 145° C. After complete conversion had beenachieved, the reaction mixture was filtered. The excess n-octanoic acidwas then removed from the resulting pale yellow reaction mixture bymeans of distillation. After adding n-hexane and further active charcoal(10 g) thee product was stirred for a further 1 hour at 80° C. Removalof the charcoal by filtration, followed by removal of the n-hexane(under reduced pressure), yielded a virtually “after-white” product.

LITERATURE REFERENCES

[0022] 1) Kobayashi T.; Mori, N.; Nishida, M.; Isobe, K.; Iwasaki, R.Surface active agent composition; Lion Corp.: Japanese PatentApplication JP-A-8-173787, 1996.

[0023] 2) Kobayashi T.; Mori, N.; Iwasaki R. Draining agent and drainingmethod; Lion Corp.: Japanese Patent Application JP-A-8-281003, 1996.

[0024] 3) Amano, H.; Yoshida, C.; Nakamura, A. Chem. Abstr.1980, 93,69076.

[0025] 4) Knightly, W. H. Preparation of baked goods; Atlas ChemicalIndustries: U.S. Pat. No. 3,394,009, 1968.

[0026] 5) Rusch, D. T. Chem. Abstr. 1971, 75, 117364

[0027] 6) Hughes, F. A. Preventing blocking of aluminium sheets; AtlasChemical Industries: U.S. Pat. No. 3,468,701, 1969.

[0028] 7) Stephen, J. F.; Smith, J. H.; Meshreki, M. H. Hinderedphenolic compounds derived from hexides as stabilizers; ICI AmericasInc: U.S. Pat. No. 4,613,638, 1986.

[0029] 8) Ochiai, M.; Ozawa, T. Chem. Abstr. 1979, 90, 209946.

[0030] 9) Kazuhisa, F. Cosmetics containing isosorbide fatty aciddiesters; Nihon Surfactants Co.: Japanese Patent ApplicationJP-59-125408, 1984.

[0031] 10) anonymous Res. Discl. 1977, 158, 45-47.

[0032] 11) Braun, D.; Bergmann, M. Angew. Macromol. Chem. 1992, 199,191-205.

[0033] 12) Le Maistre, J. W.; Ford, E. C. Epoxidized diesters ofpolyoxyethylene isosorbide; Atlas Chemical Corporation: U.S. Pat. No.3,225,067, 1965.

[0034] 13) MacKay Bremner, J. G.; Beaumont, S. Improvements in andrelating to the production of heterocyclic compounds; ICI, BritishPatent 613,444, 1946.

[0035] 14) Hayashi Kogyo Kagaku zasshi 1953, 56, 623-625.

[0036] 15) Luiues, L.; Jansen, J. Bicyclooctane derivatives asplasticisers; ATO-DLO: International Patent Application WO 99/45060(PCT/NL99/00115).

[0037] 16) Prossel, G.; Papenfuhs, B. Verfahren zur Herstellung vonMischungen aus Sorbitmonoestern, Sorbitdiestem und Partialglyceriden(Process for the preparation of mixtures of sorbitol monoesters,sorbitol diesters and partial glycerides); Clariant GmbH: EuropeanPatent Application EP 0 889 023 A1, 1999.

[0038] 17) Stuehler, H.; Kremp, E.; Oberhauser, A. Anhydroghexitolcarboxylic acid esters; Hoechst A G, German Patent Application DE 3119553, 1982.

[0039] 18) Stockburger, G. J. Process for preparing sorbitan esters; ICIAmericas Inc: U.S. Pat. No. 4,297,290, 1981.

[0040] 19) Goodwin, J. C.; Hodge, J. E.; Weisleder, D. Carbohydrate Res.1980,79, 133-141.

[0041] 20) Matyschok, H.; Ropuszynski, S. Pr. Nauk. Inst. Technol. Org.Tworzyw. Sztucznych Polytech. Wroclaw, 1973, 13, 377-387.

[0042] 21) Fleche, G.; Huchette, M. Starch 1986, 26-30.

[0043] 22) Giacometti, J.; Wolf, N.; Gomzi, Z.; Milin, C. React. Kinet.Catal. Lett. 1996, 59,. 235-240.

[0044] 23) Giacometti, J.; Milin, C.; Wolf, N.; Giacometti, F. J. Agric.Food Chem. 1996, 44, 3950-3954.

[0045] 24) Bock, K.; Pedersen, C.; Thogersen, H. Acta Chem. Scand. 1981,B 35,441-449.

1. A process for the preparation of esters of (di)anhydroglycitols byesterification of dianhydroglycitols, anhydroglycitols and/or glycitolswith alkylcarboxylic or arylcarboxylic acids containing 3 to 18 carbonatoms in the presence of an acid catalyst, characterised in that theacid catalyst is a macroporous acid ion exchange resin, and the molarratio of carboxylic acid to ((di)anhydro)glycitol is selected between 2and
 5. 2. A process according to claim 1, wherein the molar ratio ofcarboxylic acid to ((di)anhydro)glycitol is selected between 2 and
 3. 3.A process according to claim 1 or 2, wherein the water of reaction isremoved by passing a stream of inert gas through the reaction mixture.4. A process according to one of claims 1-3, wherein the reactiontemperature is between 120° C. and 180° C., in particular between 120°C. and 150° C.
 5. A process according to one of claims 1-4, wherein asulphonic acid ion exchange resin of the styrene-divinylbenzenecopolymer type is used.
 6. A process according to claim 5, wherein amacroporous ion exchange resin of the Amberlyst type is used.
 7. Aprocess according to one of claims 1-6, wherein the carboxylic acidscontain 5 to 14 carbon atoms.
 8. A process according to one of claims1-7, wherein the dianhydroglycitol is isosorbide.
 9. A process accordingto one of claims 1-8, wherein the anhydroglycitol is 1,4-sorbitan,2,5-sorbitan or 3,6-sorbitan, or a mixture of sorbitan isomers.
 10. Aprocess according to one of claims 1-9, wherein sorbitol is esterified.11. A process according to one of claims 1-10, wherein a glycitol ormonoanhydroglycitol is esterified and the reaction temperature is keptbetween 120° C. and 130° C. during the dehydration reaction of theglycitol (first step) and the reaction temperature is raised to 130° C.to 160° C. after the dehydration reaction.
 12. A process according toone of claims 1-11, wherein the reaction is carried out with activecharcoal in the reaction mixture.